Evidence map›Paper›PMID 34438113›Full record

ArticleCellular and molecular gastroenterology and hepatology2022

Delta-like 1-Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in Mouse.

Nobukatsu Horita, Theresa M Keeley, Elise S Hibdon, Elizabeth Delgado, Daniel Lafkas, Christian W Siebel, Linda C Samuelson

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Wnt regulates cellular differentiation and retinoid metabolism genes in the mouse stomach.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  2. Review
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  10. Review
  11. Differential sensitivity to Wnt signaling gradients in human gastric organoids derived from corpus and antrum.American journal of physiology. Gastrointestinal and liver physiology · 2023
    Article
  12. Gastric Stem Cell Biology and Helicobacter pylori Infection.Current topics in microbiology and immunology · 2023
    Article
  13. Cell plasticity in regeneration in the stomach and beyond.Current opinion in genetics & development · 2022
    Review
  14. Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022
    Review
  15. Review
  16. Moving Up a NOTCH: Defining the Stem Cell Niche in the Gastric Antrum.Cellular and molecular gastroenterology and hepatology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Nobukatsu HoritaDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Theresa M KeeleyDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Elise S HibdonDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Elizabeth DelgadoDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Daniel LafkasDepartment of Discovery Oncology, Genentech, San Francisco, California.
Christian W SiebelDepartment of Discovery Oncology, Genentech, San Francisco, California.
Linda C SamuelsonDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: lcsam@umich.edu.
University of Michigan · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Role of Hedgehog Signaling in Chronic Gastritis and MetaplasiaP01DK062041 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUMUCIO, DEBORAH L. · 2002 to 2017
$20.6M
University of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1M
Training in Basic and Translational Digestive SciencesT32DK094775 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN Y KAO, LINDA C. SAMUELSON · 2012 to 2026
$3.6M
Wnt Pathway Regulation of Gastric Stem Cell FunctionR01DK126451 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SAMUELSON, LINDA C. · 2022 to 2025
$2.0M
Mechanisms of Intestinal Stem Cell Injury and RepairR01DK118023 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SAMUELSON, LINDA C. · 2018 to 2021
$1.7M
Wnt pathway regulation of human gastric stem cell functionK01DK111710 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HIBDON, ELISE · 2017 to 2018
$183k
NIDDK NIH HHS K01 DK111710NIDDK NIH HHS P01 DK062041NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK118023NIDDK NIH HHS R01 DK126451NIDDK NIH HHS T32 DK094775NIGMS NIH HHS R25 GM086262
6 · The paper itself

Abstract

BACKGROUND &

aimsNotch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach.

methodsExpression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific.

resultsDelta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5

conclusionsDLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5

Indexed as

Calcium-Binding ProteinsPyloric AntrumStem CellsAnimalsCell ProliferationMiceReceptor, Notch1Receptors, NotchCalcium-Binding ProteinsDlk1 protein, mouseReceptor, Notch1Receptors, NotchGastric OrganoidsLGR5 Stem CellsNotch Inhibitory AntibodiesNotch SignalingStem Cell Niche

Identifiers

PMID34438113
PMCPMC8599166
OpenAlexW3194384945

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.